Extracellular histones promote TWIK2-dependent potassium efflux and associated NLRP3 activation in alveolar macrophages during sepsis-induced lung injury.

BACKGROUND AND AIM: Sepsis-induced acute lung injury (ALI) is a complex and life-threatening condition lacking specific and efficient clinical treatments. Extracellular histones, identified as a novel type of damage-associated molecular patterns, have been implicated in the inflammatory process of ALI. However, further elucidation is needed regarding the precise mechanism through which extracellular histones induce inflammation. The aim of this study was to investigate whether extracellular histones can activate NLRP3 inflammasome-mediated inflammation in alveolar macrophages (AMs) by affecting TWIK2-dependent potassium efflux. METHODS AND RESULTS: We conducted experiments using cecal ligation and puncture (CLP) C57BL/6 mice and extracellular histone-stimulated LPS-primed MH-S cells. The results demonstrated a significant increase in the levels of extracellular histones in the plasma and bronchoalveolar lavage fluid (BALF) of CLP mice. Furthermore, neutralizing extracellular histone mitigated lung injury and inflammation in CLP-induced ALI mice. In vitro studies confirmed that extracellular histones upregulated the expression of NLRP3 inflammasome activation-related proteins in MH-S cells, and this effect was dependent on increased potassium efflux mediated by the TWIK2 channel on the plasma membrane. Moreover, extracellular histones directly triggered a substantial influx of calcium, leading to increased Rab11 activity and facilitating the trafficking and location of TWIK2 to the plasma membrane. CONCLUSION: These findings underscore the critical role of extracellular histone-induced upregulation of TWIK2 expression on the plasma membrane of alveolar macrophages (AMs). This upregulation leads to potassium efflux and subsequent activation of the NLRP3 inflammasome, ultimately exacerbating lung inflammation and injury during sepsis.

Astrocytes in preoptic area regulate acute nociception-induced hypothermia through adenosine receptors.

AIMS: The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied. METHODS: We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation. RESULTS: Acute nociception could activate POA astrocytes and induce a decrease in body temperature. Manipulation of astrocytes allowed bidirectional control of body temperature. Furthermore, acute nociception and astrocyte activation led to increased extracellular adenosine concentration within the POA. Activation of adenosine A1 or A2A receptors contributed to decreased body temperature, while inhibition of these receptors mitigated the thermo-lowering effect of astrocytes. CONCLUSION: Our results elucidate the interplay between acute nociception and thermoregulation, specifically highlighting POA astrocyte activation. This enriches our understanding of physiological responses to painful stimuli and contributes to the analysis of the anatomical basis involved in the process.

Predicting the new psychoactive substance activity of antitussives and evaluating their ecotoxicity to fish.

The misuse of antitussives preparations is a continuing problem in the world, and imply that they might have potential new psychoactive substances (NPS) activity. However, few study focus on their ecological toxicity towards fish. In the present study, the machine learning (ML) methods gcForest and random forest (RF) were employed to predict NPS activity in 30 antitussives. The potential toxic target, mode of action (MOA), acute toxicity and chronic toxicity to fish were further investigated. The results showed that both gcForest and RF achieved optimal performance when utilizing combined features of molecular fingerprint (MF) and molecular descriptor (MD), with area under the curve (AUC) = 0.99, accuracy >0.94 and f1 score > 0.94, and were applied to screen the NPS activity in antitussives. A total of 15 antitussives exhibited potential NPS activity, including frequently-used substances like codeine and dextromethorphan. The binding affinity of these antitussives with zebrafish dopamine transporter (zDAT) was high, and even surpassing that of some traditional narcotics and NPS. Some antitussives formed hydrogen bonds or salt bridges with aspartate (Asp) 95, tyrosine (Tyr) 171 of zDAT. For the ecotoxicity, the MOA of these 15 antitussives in fish was predicted as narcosis. The prenoxdiazin, pholcodine, codeine, dextromethorphan and dextrorphan exhibited very toxic/toxic to fish. It was necessary to pay close attention to the ecotoxicity of these antitussives. In this study, the integration of ML, molecular docking and ECOSAR approaches are powerful tools for understanding the toxicity profiles and ecological hazards posed by new pollutants.

A Nationwide Study on the Risks of Complications and Healthcare Costs of Snakebite Envenomation in Taiwan.

In Taiwan, six medically important venomous snakes, Trimeresurus stejnegeri stejnegeri, Protobothrops mucrosquamatus, Deinagkistrodon acutus, Daboia siamensis, Naja atra, and Bungarus multicinctus, are found. However, comprehensive research on the complications and associated healthcare costs of snakebite envenomation (SBE) is lacking. We retrospectively analyzed pertinent information from the Taiwan National Health Insurance Research Database dated January 2002 to December 2014. We investigated the risk factors for complications and their impact on healthcare costs. Among the 12,542 patients with SBE, those from N. atra or B. multicinctus were more likely to experience wound infections and neurological complications than were those from T. s. stejnegeri or P. mucrosquamatus. In addition, being female, being elderly, and having a Charlson Comorbidity Index equal to or greater than 3 points were associated with an increased likelihood of wound infections and psychological complications. The annual national economic burden averaged US$1,083,624, with an average healthcare cost of US$1,129 per SBE. Snakebite envenomations from N. atra or B. multicinctus, as well as various complications, resulted in significantly higher costs. It is crucial to comprehend the risk factors for complications and their role in increasing expenses to provide insight for tailored healthcare interventions, mitigate complications, and reduce the economic burdens associated with SBEs.

From genetic associations to genes: methods, applications, and challenges.

Genome-wide association studies (GWASs) have identified numerous genetic loci associated with human traits and diseases. However, pinpointing the causal genes remains a challenge, which impedes the translation of GWAS findings into biological insights and medical applications. In this review, we provide an in-depth overview of the methods and technologies used for prioritizing genes from GWAS loci, including gene-based association tests, integrative analysis of GWAS and molecular quantitative trait loci (xQTL) data, linking GWAS variants to target genes through enhancer-gene connection maps, and network-based prioritization. We also outline strategies for generating context-dependent xQTL data and their applications in gene prioritization. We further highlight the potential of gene prioritization in drug repurposing. Lastly, we discuss future challenges and opportunities in this field.

Impacts of medication adherence and home healthcare on the associations between polypharmacy and the risk of severe hypoglycemia among elderly diabetic patients in Taiwan from 2002 to 2012: A nationwide case-crossover study.

AIM: To assess how medication adherence and home healthcare support influence the role of polypharmacy in induced hypoglycemia events among elderly diabetic patients. METHODS: This case-crossover study retrieved records on diabetic patients >=65 years with severe hypoglycemia from 2002 to 2012 in Taiwan. Case period defined as 1-3 days before severe hypoglycemia was compared with a preceding control period of the same length, with an all-washout period of 30 days. Moreover, the modifiable effects of medication adherence and home healthcare service use were evaluated by stratified analysis. RESULTS: Totally 2,237 patients were identified. Polypharmacy use was associated with the risk of severe hypoglycemia. Patients receiving polypharmacy without home healthcare services (aOR: 1.34; 95 % CI: 1.16-1.54) and those with poor adherence to anti-diabetic medications (aOR: 1.48; 95 % CI: 1.24-1.77) were significantly associated with an elevated risk of severe hypoglycemia. In patients with good adherence, non-home healthcare users being prescribed with polypharmacy had a higher risk of severe hypoglycemia. In the group that received home healthcare services, patients with poor adherence using polypharmacy had a higher risk of severe hypoglycemia. CONCLUSIONS: Good adherence and receiving home healthcare services were associated with a decreased odds of severe hypoglycemic events in elderly diabetic patients, regardless of the fact whether they were prescribed with polypharmacy.

Work Function Tuning of Carbon Electrode to Boost the Charge Extraction in Hole Transport Layer-Free Perovskite Solar Cells.

Perovskite solar cell (PSC) is a promising photovoltaic technology that achieves over 26% power conversion efficiency (PCE). However, the high materials costs, complicated fabrication process, as well as poor long-term stability, are stumbling blocks for the commercialization of the PSCs in normal structures. The hole transport layer (HTL)-free carbon-based PSCs (C-PSCs) are expected to overcome these challenges. However, C-PSCs have suffered from relatively low PCE due to severe energy loss at the perovskite/carbon interface. Herein, the study proposes to boost the hole extraction capability of carbon electrode by incorporating functional manganese (II III) oxide (Mn3O4). It is found that the work function (WF) of the carbon electrode can be finely tuned with different amounts of Mn3O4 addition, thus the interfacial charge transfer efficiency can be maximized. Besides, the mechanical properties of carbon electrode can also be strengthened. Finally, a PCE of 19.03% is achieved. Moreover, the device retains 90% of its initial PCE after 2000 h of storage. This study offers a feasible strategy for fabricating efficient paintable HTL-free C-PSCs.

Toward DNN of LUTs: Learning Efficient Image Restoration with Multiple Look-Up Tables.

The widespread usage of high-definition screens on edge devices stimulates a strong demand for efficient image restoration algorithms. The way of caching deep learning models in a look-up table (LUT) is recently introduced to respond to this demand. However, the size of a single LUT grows exponentially with the increase of its indexing capacity, which restricts its receptive field and thus the performance. To overcome this intrinsic limitation of the single-LUT solution, we propose a universal method to construct multiple LUTs like a neural network, termed MuLUT. Firstly, we devise novel complementary indexing patterns, as well as a general implementation for arbitrary patterns, to construct multiple LUTs in parallel. Secondly, we propose a re-indexing mechanism to enable hierarchical indexing between cascaded LUTs. Finally, we introduce channel indexing to allow cross-channel interaction, enabling LUTs to process color channels jointly. In these principled ways, the total size of MuLUT is linear to its indexing capacity, yielding a practical solution to obtain superior performance with the enlarged receptive field. We examine the advantage of MuLUT on various image restoration tasks, including super-resolution, demosaicing, denoising, and deblocking. MuLUT achieves a significant improvement over the single-LUT solution, e.g., up to 1.1dB PSNR for super-resolution and up to 2.8dB PSNR for grayscale denoising, while preserving its efficiency, which is 100× less in energy cost compared with lightweight deep neural networks. Our code and trained models are publicly available at https://github.com/ddlee-cn/MuLUT.

Functionalized electrospun nanofibers to enhance ß-Galactosidase immobilization and catalytic activity for efficient galactooligosaccharide synthesis.

This study aimed to immobilize ß-galactosidase (ß-GAL) into enhanced polystyrene (PS) electrospun nanofiber membranes (ENMs) with functionalized graphene oxide (GO). Initially, GO sheets were functionalized by salinization with 3-aminopropyl triethoxysilane (APTES). Then the ENMs (PS, PS/GO, and PS/GO-APTES) were prepared and characterized. Then, the ß-GAL was immobilized in the different ENMs to produce the ß-GAL-bound nanocomposites (PS-GAL, PS/GO-GAL, and PS/GO-APTES-GAL). Immobilization of ß-GAL into PS/GO-APTES significantly improved enzyme adsorption by up to 87 %. Also, PS/GO-APTES-GAL improved the enzyme activity, where the highest enzyme activity was obtained at enzyme concentrations of 4 mg/L, 50 °C, and pH 4.5. Likewise, the storage stability and reusability of immobilized ß-GAL were improved. Furthermore, this process led to enhanced catalytic behavior and transgalactosylation efficiency, where GOS synthesis (72 %) and lactose conversion (81 %) increased significantly compared to the free enzyme. Overall, the immobilized ß-GAL produced in this study showed potential as an effective biocatalyst in the food industry.

A rapid and simple non-radioactive assay for measuring uptake by solute carrier transporters.

Introduction: Solute carrier (SLC) transport proteins play a crucial role in maintaining cellular nutrient and metabolite homeostasis and are implicated in various human diseases, making them potential targets for therapeutic interventions. However, the study of SLCs has been limited due to the lack of suitable tools, particularly cell-based substrate uptake assays, necessary for understanding their biological functions and for drug discovery purposes. Methods: In this study, a cell-based uptake assay was developed using a stable isotope-labeled compound as the substrate for SLCs, with detection facilitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This assay aimed to address the limitations of existing assays, such as reliance on hazardous radiolabeled substrates and limited availability of fluorescent biosensors. Results: The developed assay was successfully applied to detect substrate uptakes by two specific SLCs: L-type amino acid transporter 1 (LAT1) and sodium taurocholate co-transporting polypeptide (NTCP). Importantly, the assay demonstrated comparable results to the radioactive method, indicating its reliability and accuracy. Furthermore, the assay was utilized to screen for novel inhibitors of NTCP, leading to the identification of a potential NTCP inhibitor compound. Discussion: The findings highlight the utility of the developed cell-based uptake assay as a rapid, simple, and environmentally friendly tool for investigating SLCs' biological roles and for drug discovery purposes. This assay offers a safer alternative to traditional methods and has the potential to contribute significantly to advancing our understanding of SLC function and identifying therapeutic agents targeting SLC-mediated pathways.

Pharmacological inhibition of the Src homology phosphatase 2 confers partial protection in a mouse model of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a leading factor of liver-related death worldwide. ALD has various manifestations that include steatosis, hepatitis, and cirrhosis and is currently without approved pharmacotherapies. The Src homology phosphatase 2 (Shp2) is a drug target in some cancers due to its positive regulation of Ras-mitogen-activated protein kinase signaling and cell proliferation. Shp2 pharmacological inhibition yields beneficial outcomes in animal disease models, but its impact on ALD remains unexplored. This study aims to investigate the effects of Shp2 inhibition and its validity using a preclinical mouse model of ALD. We report that the administration of SHP099, a potent and selective allosteric inhibitor of Shp2, partially ameliorated ethanol-induced hepatic injury, inflammation, and steatosis in mice. Additionally, Shp2 inhibition was associated with reduced ethanol-evoked activation of extracellular signal-regulated kinase (ERK), oxidative, and endoplasmic reticulum (ER) stress in the liver. Besides the liver, excessive alcohol consumption induces multi-organ injury and dysfunction, including the intestine. Notably, Shp2 inhibition diminished ethanol-induced intestinal inflammation and permeability, abrogated the reduction in tight junction protein expression, and the activation of ERK and stress signaling in the ileum. Collectively, Shp2 pharmacological inhibition mitigates the deleterious effects of ethanol in the liver and intestine in a mouse model of ALD. Given the multifactorial aspects underlying ALD pathogenesis, additional studies are needed to decipher the utility of Shp2 inhibition alone or as a component in a multitherapeutic regimen to combat this deadly malady.

A tempo-spatial controllable microfluidic shear-stress generator for in-vitro mimicking of the thrombus.

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.

Two-Hour Nicotine Withdrawal Improves Inhibitory Control Dysfunction in Male Smokers: Evidence from a Smoking-Cued Go/No-Go Task ERP Study.

Purpose: Nicotine withdrawal is a multifaceted physiological and psychological process that can induce a spectrum of mood disturbances. Gaining a more nuanced understanding of how pure nicotine withdrawal influences cognitive control functions may provide valuable insights for the enhancement of smoking cessation programs. This study investigated changes in inhibitory control function in smokers after 2-hour nicotine withdrawal using the event-related potential (ERP) technique. Participants and Methods: 28 nicotine dependence (ND) patients and 28 health controls (HCs) completed a smoking-cued Go/No-go task containing two different types of picture stimuli, smoking-cued and neutral picture stimuli. We analyzed the behavioral and ERP data using a mixed model Repeated Measure Analysis of Variance (ANOVA). Results: No-go trials accuracy rate (ACC) at baseline (time 1) was lower in the ND group compared to HCs with smoking-cued stimuli, and No-go trials ACC after 2-hour nicotine withdrawal (time 2) was not lower in the ND group compared to HCs. When confronted with smoking-cued stimuli, the No-go trials ACC was higher in time 2 than in time 1 in the ND group. For the ERP component, the No-go N2 amplitudes in the ND group with smoking-cued stimuli were lower than that of HCs, whereas after 2-hour nicotine withdrawal, the ND group's No-go N2 amplitudes higher than that at time 1, and did not differ from that of HCs. No-go P3 amplitudes were not significantly different between the two groups. Conclusion: Evidenced from ERP data, ND patients have an inhibitory control dysfunction in the face of smoking cues, which is mainly manifested in the early stage of response inhibition rather than in the late stage. Two-hour nicotine withdrawal improves inhibitory control dysfunction in ND patients. The No-go N2 component is an important and sensitive neuroelectrophysiological indicator of inhibitory control function in ND patients.

Limited resection is comparable to lobectomy for tumor size ≤ 2 cm pulmonary invasive mucinous adenocarcinoma.

OBJECTIVES: Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. METHODS: Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer-specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. RESULTS: In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157-5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). CONCLUSIONS: Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Association of obesity and menarche SNPs and interaction with environmental factors on precocious puberty.

BACKGROUND: Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population. METHODS: This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty. RESULTS: The effect allele C of rs571312, and G of rs12970134 MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty. CONCLUSIONS: The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention. IMPACT: This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.

Assessment of iodine nutritional status and gestational thyroid function reference ranges during the first trimester of pregnancy in Taiwan.

BACKGROUND: Iodine nutrition is critical for fetal neurodevelopment in the first trimester of pregnancy, a period associated with dramatic changes in thyroid function. The aim of this study was to evaluate iodine nutritional status and thyroid function reference ranges in the first trimester in Taiwan. METHODS: Pregnant women aged 20 years and above in the first trimester were recruited in Taipei Veterans General Hospital, Taiwan from March 2019 to July 2022. Each participant provided a spot urine sample for measurement of urinary iodine concentration (UIC) and a blood sample for check-up of thyroid function and thyroid autoantibodies. A simple food frequency questionnaire was also completed. RESULTS: A total of 209 women with a mean age of 32.9 ± 4.4 years were enrolled. The median UIC was 160.9 µg/L [interquartile range (IQR): 105.0-246.2 µg/L], indicating overall iodine sufficiency. The gestational thyroid function reference ranges were: TSH [median: 0.93 (0.007-2.9) µIU/mL], free T4 [1.3 (0.93-2.2) ng/dL], free T3 [3.0 (2.3-5.0) ng/dL], total T4 [9.9 (6.4-16.9) ng/dL] and total T3 [135 (88-231) ng/dL]. If the non-pregnant reference range of serum TSH was used, eight women (4.8%) would be misclassified as having subclinical hyperthyroidism, and two women (1.2%) with subclinical hypothyroidism would be missed. In multivariate analysis, nulliparous [adjusted odds ratio (OR) from model 1-3: 2.02, 2.05, 2.02; 95% confidence interval (CI): 1.08-3.77, 1.10-3.81, 1.11-3.66; p = 0.027, 0.023, 0.022, respectively] and multivitamin non-users (adjusted OR from model 1-3: 1.86, 1.85, 1.78; 95% CI: 1.04-3.34, 1.03-3.32, 1.004-3.71; p = 0.038, 0.039, 0.049, respectively) had increased odds of having lower UIC levels <150 µg/L. CONCLUSION: The iodine nutritional status in the first trimester is adequate in Taiwan; however, certain subgroups such as nulliparous and multivitamin non-users are still at risk for iodine deficiency. Gestational thyroid function reference ranges are needed for correct diagnosis of thyroid dysfunction in pregnancy.

Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). METHODS: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. RESULTS: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan-Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. CONCLUSION: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Surface functionalized titanium nitride electrode for CMOS compatible bioelectronic devices.

In this study, a surface functionalization approach by covalent grafting of an organic thin film containing hydroxyl groups on TiN surface via electroreduction of diazonium salts "4-(2-hydroxyethyl)benzenediazonium salt" is presented. Cyclic voltammetry procedures were carried out at the potential ranges of -0.8 V~0.5 V (vs Ag/AgCl) with varying numbers of potential cycles (i.e., 5, 25, and 50 cycles) in order to study the thickness of modification layer. Then, the electrochemical properties, surface morphology, and chemical structures of the sample before and after modifications were investigated via multiple characterization techniques, such as cyclic voltammetry (CV), atomic force microscopy (AFM), scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS), etc., thereby confirming the successful grafting of hydroxyl groups onto the TiN surface. The experiments on DNA synthesis aimed to explore the potential of modified TiN electrode as a novel platform for DNA data storage applications and the corresponding proof-of-principle was accomplished by the process of coupling Cy3-phosphoramidite. Finally, the experiments were successfully reproduced on the randomly selected sites of the modified TiN microarray chips demonstrating the potential of technical protocol to extend applications in future bioelectronic devices, such as bio-sensing, high-throughput DNA synthesis, and molecular manipulation.